Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid Research Articles

Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced magnetic resonance imaging for evaluating fibrosis regression in chronic hepatitis C patients after direct-acting antiviral.

BACKGROUNDDirect acting antiviral (DAA) therapy has enabled hepatitis C virus infection to become curable, while histological changes remain uncontained. Few valid non-invasive methods can be confirmed for use in surveillance. Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) is a liver-specific magnetic resonance imaging (MRI) contrast, related to liver function in the hepatobiliary phase (HBP). Whether Gd-EOB-DTPA-enhanced MRI can be used in the diagnosis and follow up of hepatic fibrosis in patients with chronic hepatitis C (CHC) has not been investigated. AIMTo investigate the diagnostic and follow-up values of Gd-EOB-DTPA-enhanced MRI for hepatic histology in patients with CHC.METHODSPatients with CHC were invited to undergo Gd-EOB-DTPA-enhanced MRI and liver biopsy before treatment, and those with paired qualified MRI and liver biopsy specimens were included. Transient elastography (TE) and blood tests were also arranged. Patients treated with DAAs who achieved 24-wk sustained virological response (SVR) underwent Gd-EOB-DTPA-enhanced MRI and liver biopsy again. The signal intensity (SI) of the liver and muscle were measured in the unenhanced phase (UEP) (SIUEP-liver, SIUEP-muscle) and HBP (SIHBP-liver, SIHBP-muscle) via MRI. The contrast enhancement index (CEI) was calculated as [(SIHBP-liver/SIHBP-muscle)]/[(SIUEP-liver/SIUEP-muscle)]. Liver stiffness measurement (LSM) was confirmed with TE. Serologic markers, aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4), were also calculated according to blood tests. The grade of inflammation and stage of fibrosis were evaluated with the modified histology activity index (mHAI) and Ishak fibrosis score, respectively. Fibrosis regression was defined as a ≥ 1-point decrease in the Ishak fibrosis score. The correlation between the CEI and liver pathology was evaluated. The diagnostic and follow-up values of the CEI, LSM, and serologic markers were compared.RESULTSThirty-nine patients with CHC were enrolled [average age, 42.3 ± 14.4 years; 20/39 (51.3%) male]. Twenty-one enrolled patients had eligible paired Gd-EOB-DTPA-enhanced MRI and liver tissues after achieving SVR. The mHAI median significantly decreased after SVR [baseline 6.0 (4.5-13.5) vs SVR 2.0 (1.5-5.5), Z = 3.322, P = 0.017], but the median stage of fibrosis did not notably change (P > 0.05). Sixty pairs of qualified MRI and liver tissue samples were available for use to analyze the relationship between the CEI and hepatic pathology. The CEI was negatively correlated with the mHAI (r = -0.56, P < 0.001) and Ishak score (r = -0.69, P < 0.001). Further stratified analysis showed that the value of the CEI decreased with the progression of the stage of fibrosis rather than with the grade of necroinflammation. For patients with Ishak score ≥ 5, the areas under receiver operating characteristics curve of the CEI, LSM, APRI, and FIB-4 were approximately at baseline, 0.87–0.93, and after achieving SVR, 0.83–0.91. The CEI cut-off value was stable (baseline 1.58 and SVR 1.59), but those of the APRI (from 1.05 to 0.24), FIB-4 (from 1.78 to 1.28), and LSM (from 10.8 kpa to 7.1 kpa) decreased dramatically. The APRI and FIB-4 cannot be used as diagnostic means for SVR in patients with Ishak score ≥ 3 (P > 0.05). Seven patients achieved fibrosis regression after achieving SVR. In these patients, the CEI median increased (from 1.71 to 1.83, Z = -1.981, P = 0.048) and those of the APRI (from 1.71 to 1.83, Z = -2.878, P = 0.004) and LSM (from 6.6 to 4.8, Z = -2.366, P = 0.018) decreased. However, in patients without fibrosis regression, the medians of the APRI, FIB-4, and LSM also changed significantly (P < 0.05).CONCLUSIONGd-EOB-DTPA-enhanced MRI has good diagnostic value for staging fibrosis in patients with CHC. It can be used for fibrotic-change monitoring post SVR in patients with CHC treated with DAAs.

Evaluation of Preoperative Microvascular Invasion in Hepatocellular Carcinoma Through Multidimensional Parameter Combination Modeling Based on Gd-EOB-DTPA MRI.

The study established and compared the efficacy of the clinicoradiological model, radiomics model and clinicoradiological-radiomics hybrid model in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC) using gadolinium ethoxybenzyl diethylene triaminepentaacetic acid (Gd-EOB-DTPA) enhanced MRI. This was a study that enrolled 602 HCC patients from two institutions. Least absolute shrinkage and selection operator (Lasso) method was used to screen for the most important clinicoradiological and radiomics features that predict MVI pre-operatively. Three machine learning algorithms were used to establish the clinicoradiological, radiomics, and clinicoradiological-radiomics hybrid models. Area under the curve (AUC) of receiver operating characteristic (ROC) curves and Delong's test were used to compare and quantify the predictive performance of the models. The AUCs of the clinicoradiological model in training and validation cohorts were 0.793 and 0.701, respectively. The radiomics signature of arterial phase (AP) images alone achieved satisfying predictive efficacy for MVI, with AUCs of 0.671 and 0.643 in training and validation cohort, respectively. The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images achieved AUCs of 0.824 and 0.801 in training and validation cohorts, 0.812 and 0.805 in prospective validation and external validation cohorts, respectively. The hybrid model provided the best prediction results. The results of the Delong test revealed that there were statistically significant differences among the clinicoradiological-radiomics hybrid model, clinicoradiological model, and radiomics model (p<0.05). The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images based on Gd-EOB-DTPA-enhanced MRI can effectively predict MVI.

A Potential Prognostic Marker for Recognizing VEGF-Positive Hepatocellular Carcinoma Based on Magnetic Resonance Radiomics Signature.

ObjectivesThe objective of our project is to explore a noninvasive radiomics model based on magnetic resonance imaging (MRI) that could recognize the expression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma before operation.Methods202 patients with proven single HCC were enlisted and stochastically distributed into a training set (n = 142) and a test set (n = 60). Arterial phase, portal venous phase, balanced phase, delayed phase, and hepatobiliary phase images were used to radiomics features extraction. We retrieved 1906 radiomic features from each phase of every participant’s MRI images. The F-test was applied to choose the crucial features. A logistic regression model was adopted to generate a radiomics signature. By combining independent risk indicators from the fusion radiomics signature and clinico-radiological features, we developed a multivariable logistic regression model that could predict the VEGF status preoperatively through calculating the area under the curve (AUC).ResultsThe entire group comprised 108 VEGF-positive individuals and 94 VEGF-negative patients. AUCs of 0.892 (95% confidence interval [CI]: 0.839 - 0.945) in the training dataset and 0.800 (95% CI: 0.682 - 0.918) in the test dataset were achieved by utilizing radiomics features from two phase images (8 features from the portal venous phase and 5 features from the hepatobiliary phase). Furthermore, the nomogram relying on a combined model that included the clinical factors α-fetoprotein (AFP), irregular tumor margin, and the fusion radiomics signature performed well in both the training (AUC = 0.936, 95% CI: 0.898-0.974) and test (AUC = 0.836, 95% CI: 0.728-0.944) datasets.ConclusionsThe combined model acquired from two phase (portal venous and hepatobiliary phase) pictures of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI could be considered as a credible prognostic marker for the level of VEGF in HCC.

Prediction of early recurrence of hepatocellular carcinoma after resection based on Gd-EOB-DTPA enhanced magnetic resonance imaging: a preliminary study.

Early recurrence (ER) after radical resection of hepatocellular carcinoma (HCC) affects the prognosis of patients. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can improve the detection rate of small HCC. This study innovatively introduces a new quantitative index combined with qualitative index to compare the differences in clinical and imaging characteristics between ER and non-ER groups and evaluate the feasibility of Gd-EOB-DTPA-enhanced MRI in predicting ER. A total of 68 patients with HCC confirmed by operation and pathology in the Shandong Cancer Hospital and Institute were included retrospectively. All participants were examined by Gd-EOB-DTPA-enhanced MRI within 3 weeks before surgery. Regular follow-up was performed every 2 months within 1 year after operation. Among them, 18 cases with new lesions were in ER group, and 50 cases without new lesions were in non-ER group. The clinical and imaging data of the 2 groups were collected, and the differences of clinical data and preoperative MRI signs between the ER group and non-ER group were compared. The predictive factors of ER after HCC were analyzed by multivariate logistic regression. The quantitative parameter lesion-to-liver contrast enhancement ratio (LLCER) can predict the pathological grade of HCC (P=0.023). The results of univariate analysis between the ER group and non-ER group showed that there were significant differences in pathological grade (P=0.008), lesion morphology (P=0.011), peritumoral low signal intensity in hepatobiliary phase (HBP) (P<0.001), satellite nodules (P<0.001), and LLCER (P<0.001) between the 2 groups. Multivariate logistic regression analysis showed that HBP peritumoral low signal intensity [odds ratio (OR) =7.214, 95% confidence interval (CI): 1.230-42.312, P=0.029], satellite nodules (OR =9.198, 95% CI: 1.402-60.339, P=0.021), and parameter LLCER value (OR =0.906, 95% CI: 0.826-0.995, P=0.039) were independent predictors of ER of HCC after resection. Preoperative Gd-EOB-DTPA enhanced MRI has important predictive value for early recurrence after radical resection of hepatocellular carcinoma.

Preoperative Evaluation of Gd-EOB-DTPA-Enhanced MRI Radiomics-Based Nomogram in Small Solitary Hepatocellular Carcinoma (≤3cm) With Microvascular Invasion: A Two-Center Study.

Preoperative evaluation of microvascular invasion (MVI) in small solitary hepatocellular carcinoma (HCC; maximum lesion diameter ≤ 3 cm) is important for treatment decisions. To apply gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI to develop and validate a nomogram for preoperative evaluation of MVI in small solitary HCC and to compare the effectiveness of radiomics evaluation models based on different volumes of interest (VOIs). Retrospective. A total of 196 patients include 62 MVI-positive and 134 MVI-negative patients were enrolled (training cohort, n=105; testing cohort, n=45; external validation cohort, n=46). 3.0 T, fat suppressed fast-spin-echo T2-weighted and Gd-EOB-DTPA-enhanced T1-weighted magnetization-prepared rapid gradient-echo sequences. Radiomics features were extracted on T2-weighted, arterial phase (AP), and hepatobiliary phase (HBP) images from different VOIs (VOIintratumor and VOIintratumor+peritumor ) and filtered by the least absolute shrinkage selection operator (LASSO) regression. From VOIintratumor and VOIintratumor+peritumor , eight radiomics models were constructed based on three MRI sequences (T2-weighted, AP, and HBP) and fused sequences (combined of three sequences). Nomograms were constructed of a clinical-radiological (CR) model and a clinical-radiological-radiomics (CRR) model. One-way analysis of variance, independent t-test, Chi-square test or Fisher's exact test, Wilcoxon rank-sum test, LASSO, logistic regression analysis, area under the curve (AUC), nomograms, decision curve, net reclassification improvement (NRI), integrated discrimination improvement (IDI) analyses, and DeLong test. Among eight radiomics models, the fused sequences-based VOIintratumor+peritumor radiomics model showed the best performance. The CRR model containing the best performance radiomics model and CR model with the AUC values were 0.934, 0.889, and 0.875, respectively. NRI and IDI analyses showed that the CRR model improved evaluation efficacy over the CR model for all three cohorts (all P-value <0.05). The CRR model nomogram could preoperatively evaluate MVI in small solitary HCC. The radiomics model based on VOIintratumor+peritumor might achieve better evaluation results. 4 TECHNICAL EFFICACY STAGE: 2.

A Human-derived Dual MRI/PET Reporter Gene System with High Translational Potential for Cell Tracking.

Reporter gene imaging has been extensively used to longitudinally report on whole-body distribution and viability of transplanted engineered cells. Multi-modal cell tracking can provide complementary information on cell fate. Typical multi-modal reporter gene systems often combine clinical and preclinical modalities. A multi-modal reporter gene system for magnetic resonance imaging (MRI) and positron emission tomography (PET), two clinical modalities, would be advantageous by combining the sensitivity of PET with the high-resolution morphology and non-ionizing nature of MRI. We developed and evaluated a dual MRI/PET reporter gene system composed of two human-derived reporter genes that utilize clinical reporter probes for engineered cell detection. As a proof-of-concept, breast cancer cells were engineered to co-express the human organic anion transporter polypeptide 1B3 (OATP1B3) that uptakes the clinical MRI contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), and the human sodium iodide symporter (NIS) which uptakes the PET tracer, [18F] tetrafluoroborate ([18F] TFB). T1-weighted MRI results in mice exhibited significantly higher MRI signals in reporter-gene-engineered mammary fat pad tumors versus contralateral naïve tumors (p < 0.05). No differences in contrast enhancement were observed at 5h after Gd-EOB-DTPA administration using either intravenous or intraperitoneal injection. We also found significantly higher standard uptake values (SUV) in engineered tumors in comparison to the naïve tumors in [18F]TFB PET images (p < 0.001). Intratumoral heterogeneity in signal enhancement was more conspicuous in relatively higher resolution MR images compared to PET images. Our study demonstrates the ability to noninvasively track cells engineered with our human-derived dual MRI/PET reporter system, enabling a more comprehensive evaluation of transplanted cells. Future work is focused on applying this tool to track therapeutic cells, which may one day enable the broader application of cell tracking within the healthcare system.

Gd-EOB-DTPA-enhanced MRI radiomic features for predicting histological grade of hepatocellular carcinoma.

Prediction models for the histological grade of hepatocellular carcinoma (HCC) remain unsatisfactory. The purpose of this study is to develop preoperative models to predict histological grade of HCC based on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) radiomics. And to compare the performance between artificial neural network (ANN) and logistic regression model. A total of 122 HCCs were randomly assigned to the training set (n=85) and the test set (n=37). There were 242 radiomic features extracted from volumetric of interest (VOI) of arterial and hepatobiliary phases images. The radiomic features and clinical parameters [gender, age, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), alanine aminotransferase (ALT), aspartate transaminase (AST)] were selected by permutation test and decision tree. ANN of arterial phase (ANN-AP), logistic regression model of arterial phase (LR-AP), ANN of hepatobiliary phase (ANN-HBP), logistic regression mode of hepatobiliary phase (LR-HBP), ANN of combined arterial and hepatobiliary phases (ANN-AP + HBP), and logistic regression model of combined arterial and hepatobiliary phases (LR-AP + HBP) were built to predict HCC histological grade. Those prediction models were assessed and compared. ANN-AP and LR-AP were composed by AST and radiomic features based on arterial phase. ANN-HBP and LR-HBP were composed by AFP and radiomic features based on hepatobiliary phase. ANN-AP + HBP and LR-AP + HBP were composed by AST and radiomic features based on arterial and hepatobiliary phases. The prediction models could distinguish between high-grade tumors [Edmondson-Steiner (E-S) grade III and IV] and low-grade tumors (E-S grade I and II) in both training set and test set. In the test set, the AUCs of ANN-AP, LR-AP, ANN-HBP, LR-HBP, ANN-AP + HBP and LR-AP + HBP were 0.889, 0.777, 0.941, 0.819, 0.944 and 0.792 respectively. The ANN-HBP was significantly superior to LR-HBP (P=0.001). And the ANN-AP + HBP was significantly superior to LR-AP + HBP (P=0.007). Prediction models consisting of clinical parameters and Gd-EOB-DTPA-enhanced MRI radiomic features (based on arterial phase, hepatobiliary phase, and combined arterial and hepatobiliary phases) could distinguish between high-grade HCCs and low-grade HCCs. And the ANN was superior to logistic regression model in predicting histological grade of HCC.

Prediction of microvascular invasion in HCC by a scoring model combining Gd-EOB-DTPA MRI and biochemical indicators.

This study aimed to establish a reliable diagnostic scoring model for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biochemical indicators. This retrospective study included 129 patients with HCC at our hospital from 2014 to 2020. Based on the intratumoral and peritumoral features on Gd-EOB-DTPA MRI and biochemical indicators, a scoring model was developed for preoperative prediction of MVI, and examined for diagnostic efficacy according to postoperative pathological results. The scoring model was further externally validated in an independent cohort of 63 HCC patients. Logistic regression analysis was performed to identify five parameters related to MVI, including maximum tumor diameter, peritumoral low intensity in the hepatobiliary phase, incomplete capsule, apparent diffusion coefficient (ADC), and [alkaline phosphatase (ALP) (U/L) + gamma-glutamyl transpeptidase (GGT) (U/L)] / lymphocyte count (× 109/L) ratio (AGLR). Based on these five parameters, a scoring model was developed, and the accuracy, sensitivity, specificity, PPV, and NPV in predicting MVI were 93.6%, 94.7%, 93.2%, 85.7%, and 97.6%, respectively, with a score > 8 set as the threshold. The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators provides a reliable tool for preoperative prediction of MVI in HCC patients. • The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators is practical for preoperative prediction of MVI in HCC patients. • AGLR is an independent risk factor for MVI. • The scoring model could help implement more appropriate interventions, potentially leading to precise and individualized treatments based on the biological characteristics of the tumor.

Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Living Donor Liver Transplant

Gadolinium-ethoxybenzyl-diethylene triamine pentaacetic acid (Gd-EOB-DTPA) is a newer magnetic resonance contrast that has the combined effect of conventional and liver-specific contrast. The use of Gd-EOB-DTPA may aid in management of patients with hepatocellular carcinoma (HCC) undergoing living donor liver transplant (LDLT). We retrospectively reviewed all HCC patients who received LDLT with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) as part of a pretransplant evaluation between October 2012 and October 2016. The detection rate and impact on decision making were assessed between multidetector-row computed tomography (MDCT) and Gd-EOB-DTPA-enhanced MRI with pathology of the explanted liver being the reference standard. We analyzed 25 patients with 80 nodules. Gd-EOB-DTPA-enhanced MRI showed superior detection rate for HCCs than MDCT (76.1% vs 35.8%). Among the 25 patients, 16 had additional HCCs detected by Gd-EOB-DTPA-enhanced MRI, which led to changes in therapeutic decisions in 11 patients. The recurrence rate and mortality rate were 4% (1 of 25). In the same period in our institution, the mortality rate was 13.9% (25 of 180) for those who did not receive Gd-EOB-DTPA-enhanced MRI as part of the pretransplant evaluation. The use of Gd-EOB-DTPA-enhanced MRI can aid in characterization of indeterminate nodules and detect more HCCs and thus more adequate downstaging and pretransplant neoadjuvant treatment ensue, which may lower the recurrence rate after LDLT.

Quantitative evaluation of simultaneous spatial and temporal regularization in dynamic contrast-enhanced MRI of the liver using Gd-EOB-DTPA

The purpose of this study was to quantitatively evaluate the usefulness of simultaneous spatial and temporal regularization using total variation (TV), total generalized variation (TGV), a combination of low-rank decomposition (LRD) and TV (LRD+TV), a combination of LRD and TGV (LRD+TGV), and nuclear norm (NN) when applied to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rats with concanavalin A (ConA)-induced acute hepatic injury.The rats were divided into three groups: normal control (NC) (n = 10), ConA10 (n = 8), and ConA20 (n = 7). Rats in the ConA10 and ConA20 groups were intravenously injected with 10 and 20 mg/kg of ConA, respectively; those in the NC group were intravenously injected with the same volume of saline. DCE-MRI studies were performed using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; 0.025 mmol Gd/kg) as a contrast agent (CA), 24 h after the ConA or saline injection. After the DCE-MRI study, we generated zero-filled and undersampled k-space data from the original images using a pseudoradial sampling scheme with 4 to 64 spokes. We subsequently reconstructed images from these data using the above regularizers and calculated the signal-to-error ratio (SERimg) and structural similarity index measure (SSIM) using the original and reconstructed images. We also calculated the area under the curve (AUC), rate of CA washout (λw), maximum relative enhancement (REmax), and time to REmax (Tmax) from time-intensity curves using an empirical mathematical model (EMM) and the signal-to-error ratio for curve fitting (SERfit) from the original and fit curves. We also compared the parameters obtained using the pseudoradial and Cartesian sampling schemes in the NC group.When using LRD+TV and LRD+TGV, both SERimg and SSIM were greater than those for the other regularizers at all spoke numbers studied; the SERfit for TGV was the greatest. When using TGV and LRD+TGV, in the majority of cases the AUCs did not significantly differ from those obtained from the original images, whereas those for LRD+TV and NN were significantly less at several spoke numbers. The λw for NN was significantly greater at numerous spoke numbers in the NC group; the REmax values for LRD+TV and NN were significantly less at several spoke numbers in all groups. The Tmax values for TV, TGV, and LRD+TGV were significantly greater at numerous spoke numbers in the NC group. Although there were significant differences in SERimg and SSIM between the pseudoradial and Cartesian sampling schemes, the kinetic parameters obtained by the EMM did not significantly differ between the two sampling schemes, with certain exceptions.In conclusion, our results suggest that simultaneous spatial and temporal regularization using TGV or LRD+TGV is useful for accelerating DCE-MRI without significant reduction in the accuracy of the kinetic parameter estimation, even at extremely low sampling factors.

Comparing the CT and MRI findings for canine primary hepatocellular lesions.

Triple-phase CT and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI have been used to differentiate hepatocellular carcinomas (HCCs) in dogs. This retrospective case series aimed to compare the CT findings with MRI findings of 20 canine hepatocellular lesions, including eight poorly/moderately-differentiated HCCs, eight well-differentiated HCCs and four hyperplasias. CT data were analysed, and the following parameters were noted: vessel enhancement, enhancement pattern in the equilibrium phase, maximal transverse diameter, the lowest enhancement, and the attenuation values of each hepatocellular lesion in the precontrast and triple-phase series, including the arterial phase, portal phase and equilibrium phase. MRI data were analysed, and the following parameters were noted: signal intensities of each hepatocellular lesion on T2-weighted images and T1-weighted images, and signal intensity ratio of the hepatocellular lesions in the hepatobiliary phase. In 62.5% of poorly/moderately-differentiated HCC and 75% of well-differentiated HCC, presumptive necrosis was detected on CT and MRI. In the hepatobiliary phase on MRI, the median signal intensity ratio of poorly/moderately-differentiated HCC (0.54 [range: 0.3-0.71]) was significantly lower than that of well-differentiated HCC (0.75 [range: 0.6-0.96]) and hyperplasia (0.79 [range: 071-0.98]; p=0.02 and p=0.02, respectively). Gd-EOB-DTPA-enhanced MRI may be a superior modality for differentiating hepatocellular origin lesions.

Risk stratification of hepatocellular carcinoma in patients with chronic liver disease by combining gadolinium‐ethoxybenzyl diethylenetriamine‐pentaacetic acid–enhanced magnetic resonance imaging and magnetic resonance elastography

Background Liver stiffness (LS) as measured by magnetic resonance elastography (MRE) and the presence of intrahepatic nonhypervascular hypointense nodules (NHHNs) during the hepatobiliary phase of gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid–enhanced magnetic resonance imaging are non-invasive MR-based biomarkers of hepatocarcinogenesis. Methods We retrospectively evaluated the ability of these two MR-based biomarkers to stratify the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. Between September 2013 and April 2020, 868 consecutive patients underwent MRE and gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid–enhanced magnetic resonance imaging, among whom 487 were enrolled in this study. Factors associated with hepatocarcinogenesis were analysed by a Cox proportional hazard model. Results Thirty-two patients developed hypervascular HCC. According to the time-dependent receiver operating characteristic analysis, an LS value of 3.94 kPa was selected as the optimal cut-off value for predicting HCC development. Multivariate analyses identified high LS (≥3.94 kPa) and the presence of NHHN as independent predictive factors for HCC development. Patients were classified as follows: high LS/NHHN+ (Group 1), high LS/NHHN− (Group 2), low LS/NHHN+ (Group 3) and low LS/NHHN− (Group 4). The 5-year incidence rates of HCC in Groups 1, 2, 3 and 4 were 49.0%, 16.3%, 10.0% and 2.5% respectively. The HCC development rate was highest in Group 1 and lowest in Group 4 (P < 0.01). Conclusion MRE-based LS measurements and the presence of NHHN are useful biomarkers to stratify the risk of HCC development among chronic liver disease patients. Combining these biomarkers can provide a detailed classification of the risk of HCC development.

Diagnosis of Hepatocellular Carcinoma Using Gd-EOB-DTPA MR Imaging.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Gadoxetic acid; Gadoxetate disodium) is a hepatocyte-specific MR contrast agent. It acts as an extracellular contrast agent in the early phase after intravenous injection, and then is taken up by hepatocytes later. Using this contrast agent, we can evaluate the hemodynamics of the liver and liver tumors, and can therefore improve the detection and characterization of hepatocellular carcinoma (HCC). Gd-EOB-DTPA helps in the more accurate detection of hypervascular HCC than by other agents. In addition, Gd-EOB-DTPA can detect hypovascular HCC, which is an early stage of the multi-stage carcinogenesis, with a low signal in the hepatobiliary phase. In addition to tumor detection and characterization, Gd-EOB-DTPA contrast-enhanced MR imaging can be applied for liver function evaluation and prognoses evaluation. Thus, Gd-EOB-DTPA plays an important role in the diagnosis of HCC. However, we have to employ optimal imaging techniques to improve the diagnostic ability. In this review, we aimed to discuss the characteristics of the contrast media, optimal imaging techniques, diagnosis, and applications.

Liver Fibrosis Staging with Gadolinium Ethoxybenzyl Diethylenetriamine Penta-Acetic Acid-enhanced: A Systematic Review and Meta-analysis.

While liver biopsy is the golden standard for liver-fibrosis diagnosis, it is also invasive and has many limitations. Non-invasive techniques such as Magnetic Resonance Imaging (MRI) need to be further developed for liver fibrosis staging. This study aimed to evaluate the diagnostic accuracy of Gadolinium Ethoxybenzyl Diethylenetriamine Penta-acetic Acid (Gd-EOBDTPA)- enhanced MRI for liver fibrosis through systematic review and meta-analysis. This study comprehensively searched relevant article in PubMed, Embase, and the Cochrane Library published from 2004 to 2018 to find studies analyzing the diagnostic accuracy of Gd-EOB-DTPA-enhanced MRI for liver fibrosis. Two reviewers independently screened the retrieved articles, extracted the required data from the included studies, and evaluated the methodological quality of the studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and Summary Receiver Operating Characteristics (SROC) curve were assessed. This study finally included 16 studies (n = 1,599) and selected a random-effects model based on the results of the I2 statistic to combine them. The areas under the SROC curve for the detection of F1 or greater, F2 or greater, F3 or greater, or F4 liver fibrosis were 0.8669, 0.8399, 0.8481, and 0.8858, respectively. Gd-EOB-DTPA-enhanced MRI showed a good diagnostic performance for staging liver fibrosis, especially for F4 liver fibrosis.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced T1 mapping to evaluate liver damage caused by Clonorchis sinensis

OBJECTIVE: The objective of the study is to explore the feasibility of Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) T1 mapping for evaluating liver damage caused by Clonorchis sinensis infection in rabbit models. MATERIALS AND METHODS: Forty-two rabbits were randomly divided into a control group (n = 10), mild infection group (n = 12), moderate infection group (n = 9), and severe infection group (n = 11). All rabbits underwent an magnetic resonance imaging scan and pathological examination to obtain the relaxation time before Gd-EOB-DTPA enhancement and the relaxation time after Gd-EOB-DTPA enhancement at intervals of 10, 15, 20, 25, 30, 35, and 40 min. The Ishak score was used to evaluate the inflammation and fibrosis of the liver. RESULTS: The severity of C. sinensis infection was positively correlated with liver inflammation. The T1 relaxation time of liver increased with increasing inflammation. The highest correlation was recorded between inflammation and the T1 relaxation time at 30 min (P = 0.001). After enhancement, The T1 relaxation time has a significant difference between the severe infection group and control group and between the severe infection group and mild infection group. The area under the receiver operating characteristics curve showed that the T1 relaxation time was the most effective parameter for diagnosing the degree of inflammation at 30 min. CONCLUSIONS: Gd-EOB-DTPA-enhanced T1 mapping can be used to evaluate the liver damage caused by C. sinensis infection.

A long-term survivor of metachronous liver metastases of pancreatic serous cystic neoplasm associated with von Hippel\u2013Lindau disease

BackgroundPancreatic serous cystic neoplasm (SCN) is an uncommon exocrine neoplasm, which is believed to be a benign entity. However, some of these neoplasms may occasionally attain metastatic ability. Von Hippel–Lindau disease (VHL) manifests a dominantly inherited systemic syndrome accompanied by several benign or malignant tumors, including cystic tumors, in various organs. We describe here a long-term survival case who underwent surgical resection for metachronous liver metastases of pancreatic SCN associated with VHL disease.Case presentationA 35-year-old woman with VHL underwent total pancreatectomy and right nephrectomy for pancreatic SCN and renal cell carcinoma, respectively. At the 4th year follow-up examination after the resection, contrast-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) showed arterially hyper-enhanced neoplastic lesions in the segment VI and VIII of the liver. Partial resections of the liver were performed 53 months after the initial surgery. At the 6th month follow-up examination from the second surgery, one and two tumors located in the liver segment III, and VIII, respectively, were detected by contrast-enhanced CT and Gd-EOB-DTPA-enhanced MRI. Anterior segmentectomy and partial resection of the segment III were performed 66 months after the initial surgery and 13 months after the second, respectively. The tumors were pathologically diagnosed as liver metastases of pancreatic SCN synonymous with serous cystadenocarcinoma. She remains disease-free without recurrence 6.5 years after the last operation.ConclusionsThis is the first report of a case of metastatic SCN associated with VHL. Surgical resection might confer a favorable prognosis in patients of pancreatic SCN with liver metastases.

Radiomic analysis of Gd-EOB-DTPA-enhanced MRI predicts Ki-67 expression in hepatocellular carcinoma

BackgroundNuclear protein Ki-67 indicates the status of cell proliferation and has been regarded as an attractive biomarker for the prognosis of HCC. The aim of this study is to investigate which radiomics model derived from different sequences and phases of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was superior to predict Ki-67 expression in hepatocellular carcinoma (HCC), then further to validate the optimal model for preoperative prediction of Ki-67 expression in HCC.MethodsThis retrospective study included 151 (training cohort: n = 103; validation cohort: n = 48) pathologically confirmed HCC patients. Radiomics features were extracted from the artery phase (AP), portal venous phase (PVP), hepatobiliary phase (HBP), and T2-weighted (T2W) images. A logistic regression with the least absolute shrinkage and selection operator (LASSO) regularization was used to select features to build a radiomics score (Rad-score). A final combined model including the optimal Rad-score and clinical risk factors was established. Receiver operating characteristic (ROC) curve analysis, Delong test and calibration curve were used to assess the predictive performance of the combined model. Decision cure analysis (DCA) was used to evaluate the clinical utility.ResultsThe AP radiomics model with higher decision curve indicating added more net benefit, gave a better predictive performance than the HBP and T2W radiomic models. The combined model (AUC = 0.922 vs. 0.863) including AP Rad-score and serum AFP levels improved the predictive performance more than the AP radiomics model (AUC = 0.873 vs. 0.813) in the training and validation cohort. Calibration curve of the combined model showed a good agreement between the predicted and the actual probability. DCA of the validation cohort revealed that at a range threshold probability of 30–60%, the combined model added more net benefit compared with the AP radiomics model.ConclusionsA combined model including AP Rad-score and serum AFP levels based on enhanced MRI can preoperatively predict Ki-67 expression in HCC.

Multichannel three-dimensional fully convolutional residual network-based focal liver lesion detection and classification in Gd-EOB-DTPA-enhanced MRI.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has high diagnostic accuracy in the detection of liver lesions. There is a demand for computer-aided detection/diagnosis software for Gd-EOB-DTPA-enhanced MRI. We propose a deep learning-based method using one three-dimensional fully convolutional residual network (3D FC-ResNet) for liver segmentation and another 3D FC-ResNet for simultaneous detection and classification of a focal liver lesion in Gd-EOB-DTPA-enhanced MRI. We prepared a five-phase (unenhanced, arterial, portal venous, equilibrium, and hepatobiliary phases) series as the input image sets and labeled focal liver lesion (hepatocellular carcinoma, metastasis, hemangiomas, cysts, and scars) images as the output image sets. We used 100 cases to train our model, 42 cases to determine the hyperparameters of our model, and 42 cases to evaluate our model. We evaluated our model by free-response receiver operating characteristic curve analysis and using a confusion matrix. Our model simultaneously detected and classified focal liver lesions. In the test cases, the detection accuracy for whole focal liver lesions had a true-positive ratio of 0.6 at an average of 25 false positives per case. The classification accuracy was 0.790. We proposed the simultaneous detection and classification of a focal liver lesion in Gd-EOB-DTPA-enhanced MRI using multichannel 3D FC-ResNet. Our results indicated simultaneous detection and classification are possible using a single network. It is necessary to further improve detection sensitivity to help radiologists.

The value of the signal intensity of peritumoral tissue on Gd-EOB-DTPA dynamic enhanced MRI in assessment of microvascular invasion and pathological grade of hepatocellular carcinoma.

The aim of the study was to assess the potential role of preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) dynamic enhanced MR imaging for diagnosing microvascular invasion (MVI) and pathological grade of hepatocellular carcinoma (HCC).A total of 113 consecutive HCC patients confirmed by histopathology underwent preoperative Gd-EOB-DTPA dynamic enhanced MRI were included. Signal intensity (SI) of peritumoral, normal liver tissue and tumor parenchyma during arterial phase and hepatobiliary phase (HBP) were analyzed. The receiver operating characteristic (ROC) curves were performed to assess the potential diagnostic capability for MVI and pathological grade of HCC. Kaplan–Meier method was performed to estimate the recurrence-free survival rate and compared using the log rank test.SI ratio of peritumoral tissue to normal liver in arterial phase (SIAp/Al) was independently associated with MVI [odds ratio (OR) = 3.115, 95% confidence interval (CI): 1.867–5.198] and pathological grades (OR = 1.437, 95% CI: 1.042–1.981). The area under the curve (AUC) of SIAp/Al was equivalent to the SI of tumor parenchyma on arterial phase (SIAt) in distinguishing low and high pathological grades. However, the AUC of SIAp/Al (0.851) was larger than peritumoral hypointensity on HBP (0.668) for distinguishing MVI. The recurrence-free survival rate of HCC patients with SIAp/Al<1.1 was higher than HCC with SIAp/Al≥1.1(P = .025).The SIAp/Al in preoperative Gd-EOB-DTPA dynamic enhanced MR imaging is a potential diagnosis marker for MVI and pathological grade of HCC noninvasively. The higher SIAp/Al may predict the poor prognosis of HCC after surgery.

Texture Analysis Based on Gd-EOB-DTPA-Enhanced MRI for Identifying Vessels Encapsulating Tumor Clusters (VETC)-Positive Hepatocellular Carcinoma.

PurposeTo determine the potential findings associated with vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma (HCC), with particular emphasis on texture analysis based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI.MethodsEighty-one patients with VETC-negative HCC and 52 patients with VETC-positive HCC who underwent Gd-EOB-DTPA-enhanced MRI before curative partial hepatectomy were retrospectively evaluated in our institution. MRI texture analysis was performed on arterial phase (AP) and hepatobiliary phase (HBP) images. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to select texture features most useful for identifying VETC-positive HCC. Univariate and multivariate analyses were used to determine significant variables for identifying the VETC-positive HCC in clinical factors and the texture features of MRI. Receiver operating characteristic (ROC) analysis and DeLong test were performed to compare the identified performances of significant variables for identifying VETC-positive HCC.ResultsLASSO logistic regression selected 3 features in AP and HBP images, respectively. In multivariate analysis, the Log-sigma-4.0-mm-3D first-order Kurtosis derived from AP images (odds ratio [OR] = 4.128, P = 0.001) and the Wavelet-LHL-GLDM Dependence Non Uniformity Normalized derived from HBP images (OR = 2.280, P = 0.004) were independent significant variables associated with VETC-positive HCC. The combination of the two texture features for identifying VETC-positive HCC achieved an AUC value of 0.844 (95% confidence interval CI, 0.777, 0.910) with a sensitivity of 80.8% (95% CI, 70.1%, 91.5%) and specificity of 74.1% (95% CI, 64.5%, 83.6%).ConclusionTexture analysis based on Gd-EOB-DTPA-enhanced MRI can help identify VETC-positive HCC.